# A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer

Source: https://onco.cc/key-papers/paper-espac-1-chemoradiotherapy-chemotherapy-resected-pancreatic-nejm-2004/  
OnCo record `paper-espac-1-chemoradiotherapy-chemotherapy-resected-pancreatic-nejm-2004` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The 2004 European trial that showed chemotherapy after pancreatic cancer surgery doubled five-year survival, while adding radiotherapy to the chemotherapy made survival worse, a result that split European and American practice for a decade.

## Summary

ESPAC-1 used a two-by-two factorial design to randomise 289 patients with resected pancreatic ductal adenocarcinoma: 73 to chemoradiotherapy alone (20 Gy over two weeks plus fluorouracil), 75 to chemotherapy alone (fluorouracil), 72 to both and 69 to observation. With 237 deaths and a median follow-up of 47 months, the estimated five-year survival was 10 percent among patients assigned chemoradiotherapy and 20 percent among those who did not receive it (P = 0.05), and 21 percent among those who received chemotherapy against 8 percent among those who did not (P = 0.009); the chemotherapy benefit persisted after adjustment for prognostic factors. The authors concluded that adjuvant chemotherapy has a significant survival benefit whereas adjuvant chemoradiotherapy has a deleterious effect.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: pancreatic-evidence
- Journal: New England Journal of Medicine
- Year: 2004
- DOI: 10.1056/NEJMoa032295
- Authors: Neoptolemos JP, Stocken DD, Friess H, et al.
- Findings: 289 resected patients in a two-by-two factorial design; 237 deaths at 47 months median follow-up.; Five-year survival 21 percent with chemotherapy against 8 percent without (P = 0.009).; Five-year survival 10 percent with chemoradiotherapy against 20 percent without (P = 0.05).
- What it means: The origin of the European position that adjuvant treatment means chemotherapy alone; CONKO-001, ESPAC-3, ESPAC-4 and PRODIGE 24 all built on it, and the role of radiotherapy remains contested (LAP07, PREOPANC).
- Caveats: The factorial design allowed clinician choice of randomisation options and background treatment, criticised at the time.; Split-course radiotherapy at 20 Gy is not modern chemoradiotherapy; the harm may not generalise.

## Sources

- N Engl J Med 2004: https://doi.org/10.1056/NEJMoa032295
- PubMed: https://pubmed.ncbi.nlm.nih.gov/15028824/

## Connected records

- key papers: [Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial](https://onco.cc/key-papers/paper-conko-001-adjuvant-gemcitabine-observation-jama-2007/), [ESPAC-3: adjuvant fluorouracil plus folinic acid versus gemcitabine after pancreatic cancer resection](https://onco.cc/key-papers/paper-espac-3-fluorouracil-vs-gemcitabine-adjuvant-neoptolemos-jama-2010/)
- roadmaps: [Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs](https://onco.cc/roadmaps/chemotherapy-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)
- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Radiation Therapy](https://onco.cc/fronts/radiation/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/)
- drugs: [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/)
- terms: [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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